OBJECTIVE: Diminished suppression of the P50 auditory evoked potential is a widely used sensory gating phenotype in the molecular genetic studies of schizophrenia. The aim of this study was to explore the relationship between this phenotype and neuregulin 1-related intracellular signaling processes. METHOD: The P50 evoked potential was recorded in 30 first-episode, never-medicated patients with schizophrenia and in 30 healthy comparison volunteers. Neuregulin 1-induced activation of the phosphoinositide 3'-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta system was characterized by the measurement of the phosphorylated AKT to total AKT ratio in peripheral B lymphoblasts. RESULTS: Relative to comparison subjects, patients with first-episode schizophrenia displayed diminished P50 suppression and decreased neuregulin 1-induced AKT phosphorylation. There was a significant relationship between P50 suppression and AKT phosphorylation. CONCLUSION: Decreased neuregulin 1-induced activation of the PI3K/AKT system is associated with impaired sensory gating in first-episode schizophrenia.
OBJECTIVE: Diminished suppression of the P50 auditory evoked potential is a widely used sensory gating phenotype in the molecular genetic studies of schizophrenia. The aim of this study was to explore the relationship between this phenotype and neuregulin 1-related intracellular signaling processes. METHOD: The P50 evoked potential was recorded in 30 first-episode, never-medicated patients with schizophrenia and in 30 healthy comparison volunteers. Neuregulin 1-induced activation of the phosphoinositide 3'-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta system was characterized by the measurement of the phosphorylated AKT to total AKT ratio in peripheral B lymphoblasts. RESULTS: Relative to comparison subjects, patients with first-episode schizophrenia displayed diminished P50 suppression and decreased neuregulin 1-induced AKT phosphorylation. There was a significant relationship between P50 suppression and AKT phosphorylation. CONCLUSION: Decreased neuregulin 1-induced activation of the PI3K/AKT system is associated with impaired sensory gating in first-episode schizophrenia.
Authors: N Takahashi; T Sakurai; O Bozdagi-Gunal; N P Dorr; J Moy; L Krug; M Gama-Sosa; G A Elder; R J Koch; R H Walker; P R Hof; K L Davis; J D Buxbaum Journal: Transl Psychiatry Date: 2011-05-10 Impact factor: 6.222